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A 45-year-old man with a history of horseshoe kidney was noted to have a right renal mass by CT scan. A partial nephrectomy specimen contained a 4.0 cm encapsulated tan/red friable mass in the upper pole, which appeared confined to the kidney. The tumor cells were cytokeratin (+), synaptophysin (+) and chromogranin (+).

Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2007, Case 7 and is a carcinoid tumor.

Criteria for Diagnosis and Comments:
Primary renal carcinoid tumors are rare with about 40 cases reported in the English literature. Before one accepts the possibility of a primary renal carcinoid tumor, metastasis from another more common site should be excluded (gastrointestinal, pulmonary, etc.). The clinical presentation is often nonspecific with abdominal pain and hematuria as the most common symptoms. Carcinoid syndrome may infrequently occur. These tumors have shown a wide age range from 13-79 years, but most occur in middle aged adults. There does not appear to be a gender predominance.

Renal carcinoids are grossly well circumscribed, yellow to tan-white, and have ranged in size from 1-30 cm (average size 10 cm). The tumors are generally solid but may show cystic change, calcification or foci of hemorrhage. This case demonstrates the typical morphologic features of carcinoid tumor characterized by a predominantly trabecular growth pattern within a vascularized stroma. The cells contain round, regular nuclei with “salt and pepper“ chromatin, some with inconspicuous nucleoli. Some slides from this case also show foci of lymphovascular invasion.

The immunophenotype is similar to carcinoid tumors arising elsewhere with expression of cytokeratin and neuroendocrine markers including chromogranin, synaptophysin and NSE. Some tumors have also shown additional expression of polypeptide neuroendocrine markers (e.g., pancreatic polypeptide, serotonin and glucagon) and a few cases have shown positive staining for prostatic acid phosphatase similar to hindgut carcinoids.

A number of renal carcinoid tumors have been associated with presence of a horseshoe kidney (a congenital malformation that results in the fusion of the kidney poles, usually inferiorly). Of 40 cases, eight have had origin in horseshoe kidneys and there appears to be an increased risk of development of carcinoid tumor as compared to normal kidneys. Although early reports of carcinoids arising in horseshoe kidneys were organ confined, possibly suggesting a more indolent course as compared to those in normal kidneys, it should be noted that several subsequent cases were associated with metastatic disease.

Approximately 25% of all cases have resulted in metastatic disease most commonly to lymph nodes or liver. Even so, some of these cases have had a long protracted clinical course. The histologic features do not predict outcome, although mitotic activity and pleomorphism were more prominent in tumors that metastasized in one series.

Papillary renal cell carcinoma is a subtype of renal cell carcinoma that appears to have a better prognosis than the more common clear cell variant. The histologic appearance of papillae often with foamy macrophages within the fibrovascular cores is characteristic. The trabecular pattern in this case is not typical of papillary RCC nor is the expression of neuroendocrine markers.

Metanephric adenoma is a predominantly benign lesion with a tendency to occur in young to middle age women. Histologically, the lesion is characterized by packed monotonous small tubules with only scant stroma and often shows psammomatous calcification. Tumors that demonstrate a biphasic appearance with both epithelial and spindle cell components are designated as metanephric adenofibromas. The cells are generally bland without atypia or mitotic activity and histologic confusion with carcinoid is unlikely. Immunophenotypically, the tumors are negative for neuroendocrine markers and are positive for Wilms tumor protein antigen (WT1).

Paragangliomas have rarely been described in the kidney and one might entertain this possibility especially in a small biopsy showing a nested pattern that may be seen in some carcinoids. Paragangliomas demonstrate expression of neuroendocrine markers but are negative for epithelial markers such as cytokeratin. Usually the typical histology of cell clusters “zellballen” associated with a sustentacular network (highlighted by antibodies to S100 protein) are features that distinguish them from carcinoid tumor.

Renal oncocytomas are benign tumors often discovered as an asymptomatic mass or masses (oncocytosis) during patient evaluation for other conditions. Although oncocytic change has been described in carcinoids, including those in the kidney, the characteristic gross mahogany-brown coloration with presence of a central stellate scar and histologic features of compact nests of polygonal cells with abundant granular eosinophilic cytoplasm within a loose myxoid stroma would help differentiate oncocytoma from carcinoid tumor. Renal oncocytomas are negative for neuroendocrine markers.